Evaluation of the Safety and Efficacy of Immunotherapy Rechallenge in Patients With Renal Cell Carcinoma
Open Access
- 1 October 2020
- journal article
- conference paper
- Published by American Medical Association (AMA) in JAMA Oncology
- Vol. 6 (10), 1606-1610
- https://doi.org/10.1001/jamaoncol.2020.2169
Abstract
ImportanceSeveral immune checkpoint inhibitors (ICIs) are approved for use in patients with metastatic renal cell carcinoma (mRCC), but the efficacy and safety of ICI rechallenge in mRCC is unknown. ObjectiveTo evaluate the safety and efficacy of ICI rechallenge in patients with mRCC. Design, Setting, and ParticipantsThis multicenter, retrospective cohort study included consecutive patients with mRCC from 9 institutions in the US who received at least 2 separate lines of ICI (ICI-1, ICI-2) between January 2012 and December 2019. ExposureReceipt of an ICI (anticytotoxic T-lymphocyte-associated protein 4, anti-programmed cell death protein 1, or anti-programmed cell death ligand 1), alone or in combination with other therapies, in at least 2 separate lines of therapy for mRCC. Main Outcomes and MeasuresInvestigator-assessed best overall response and immune-related adverse events. ResultsA total of 69 patients were included. Median (range) age at diagnosis of mRCC was 61 (36-86) years. Of these, 50 were men and 19 were women. The most common therapies received at ICI-1 were single-agent ICI (n=27 [39%]) or ICI in combination with targeted therapy (n=29 [42%]), while at ICI-2, the most common therapies were single-agent ICI (n=26 [38%]) or dual ICI (n=22 [32%]). Most patients discontinued ICI-1 owing to disease progression (n=50 [72%]) or toxic effects (n=16 [23%]). The overall response rates at ICI-1 and ICI-2 were 37% and 23%, respectively. The likelihood of a response at ICI-2 was greatest among patients who had previously responded to ICI-1 (7 of 24 [29%]), although responses at ICI-2 were seen in those who had progressive disease as their best response following ICI-1 (3 of 14 [21%]) as well as in those who received single-agent ICI at ICI-2 (7 of 23 [30%]). Grade 3 or higher immune-related adverse events were seen in 18 patients (26%) and 11 patients (16%) at ICI-1 and ICI-2, respectively. There were no treatment-related deaths. Conclusions and RelevanceThe findings of this multicenter cohort study suggest that ICI rechallenge in patients with mRCC may be safe and reasonably efficacious, with an overall response rate of 23%. Data from prospective studies are needed to validate these findings and determine the role of sequential ICI regimens in treatment of mRCC.This publication has 15 references indexed in Scilit:
- Tailored immunotherapy approach with nivolumab in advanced renal cell carcinoma (TITAN-RCC)Annals of Oncology, 2019
- Retreatment With Anti-PD-L1 Antibody in Advanced Non-small Cell Lung Cancer Previously Treated With Anti-PD-1 AntibodiesAnticancer Research, 2019
- Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell CarcinomaThe New England Journal of Medicine, 2019
- Ipilimumab plus nivolumab (Ipi/Nivo) as salvage therapy in patients with immunotherapy (IO)-refractory metastatic renal cell carcinoma (mRCC).Journal of Clinical Oncology, 2019
- Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumorsAnnals of Oncology, 2019
- Response to single agent PD-1 inhibitor after progression on previous PD-1/PD-L1 inhibitors: a case seriesJournal for ImmunoTherapy of Cancer, 2017
- Faculty Opinions recommendation of Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.Published by H1 Connect ,2016
- Nivolumab versus Everolimus in Advanced Renal-Cell CarcinomaThe New England Journal of Medicine, 2015
- Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trialThe Lancet Oncology, 2015
- Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trialThe Lancet Oncology, 2015